The induction of leukemia-lymphosarcoma complex (LLC) in domestic cats by the feline leukemia virus (FeLV) provides an especially useful model with which to examine the general process of non-defective retroviral mediated oncogenesis. Our understanding of this process will be amplified by determining the molecular events responsible for this type of neoplasia at the nucleic acid level. In this proposal we will systematically evaluate the structure and location of exogenously acquired FeLV proviruses in pathologically defined tumors animals displaying LLC disease Using specific subgenomic hybridization probes that react with only the exgenously acquired subtypes A, B, and C FeLV proviruses, the overall organization of FeLV proviruses will be determined from a representative number of FeLV positive lymphosarcomas. A small number of independently isolated lymphosarcomas, displaying a low proviral copy number and having monoclonal integration sites will be examined more closely using recombinant DNA methodology. The major structural features of tumor specific cloned provirus will be established by restriction enzyme site mapping and electron microscopic heteroduplex techniques. The 6-10 of host DNA sequences proximal to each provirus will be examined for commonality with similar host DNA sequence flanking the proviruses of the other tumors. Lastly, we will begin gene transfer (transfection) experiments to directly clone the feline oncornavirus-association cell membrane antigen (FOCMA) genes. We will carry out this study by transfecting a viral negative recombinant DNA library in the presence of limiting amounts of the Herpes Virus tk gene onto mouse tk- cells. Transfected cells expressing FOCMA determinant will be detected by indirect immonfluorescence and isolated by cell sorting. The long term goals of this project are to further our knowledge of the molecular changes that effect neoplastic transformation and to understand the mechanism(s) of induction of cell surfaces antigens.